| The levels of both decorin and transforming growth factor beta (TGF-β) are increased in the process of osteoarthritis (OA). TGF-β, one of the major growth factors, plays an important role in the maintenance of the extracellular matrix (ECM) of the articular cartilage. Decorin, a small proteoglycan, can bind to TGF-β; therefore, it may regulate TGF-β's function. The combined effect of TGF-β and decorin on chondrocytes is unclear, and it is essential to elucidate the consequences of their interaction. We hypothesized that increased decorin levels will result in the binding of more TGF-β. This may cause abrogation of the effect of TGF-β on chondrocytes, including the synthesis of the major matrix molecules, and may lead to a shift in the biological processes that are necessary for the maintenance of the homeostasis of the cartilage matrix.; Chondrocytes derived from human ankle joints were cultured in alginate beads, and the effects of TGF-β, decorin and the combination of these two regulators were studied. TGF-β significantly enhanced the mRNA levels of aggrecan, link protein and type II collagen, while the mRNA levels of small proteoglycans were moderately increased (measured by semi-quantitative reverse transcription-polymerase chain reactions). The protein contents of aggrecan (characterized by dimethylmethylene blue assay), link protein, biglycan and fibromodulin (determined by immunopreciptation and Western blot hybridization) were increased by TGF-β. The effect of TGF-β on aggrecan, link protein, and type II collagen was abrogated by exogenous recombinant human (rh) decorin, whereas the effect of TGF-β on small proteoglycans was not affected. To address these unexpected results, the effect of rh decorin on chondrocytes was determined. Decorin decreased the expression levels of aggrecan, link protein and type II collagen, but had no effect on the expression of small proteoglycans. Taken together, decorin binds to TGF-β, and the decorin-bound TGF-β is still able to regulate the metabolism of chondrocytes. Moreover, decorin and TGF-β express their own effects independent of each other. Therefore, decorin can counteract the effect of TGF-β, not through binding to it and thereby preventing TGF-β from binding to its receptors, but by expressing opposite effects on chondrocytes. This should be considered in the study and treatment of OA. |
